scholarly journals Role of alanine:glyoxylate aminotransferase 2 in metabolism of asymmetric dimethylarginine in the settings of asymmetric dimethylarginine overload and bilateral nephrectomy

2014 ◽  
Vol 29 (11) ◽  
pp. 2035-2042 ◽  
Author(s):  
Roman N. Rodionov ◽  
Jens Martens-Lobenhoffer ◽  
Silke Brilloff ◽  
Bernd Hohenstein ◽  
Natalia Jarzebska ◽  
...  
Keyword(s):  
Asymmetric Dimethylarginine ◽  
Bilateral Nephrectomy ◽  
Alanine:Glyoxylate Aminotransferase

Abstract 219: Agxt2 Plays Important Role in Regulation of Urine Adma Levels After Acute Adma Loading in Mice

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Roman N Rodionov ◽  
Jens Martens-Lobenhoffer ◽  
Silke Brilloff ◽  
Bernd Hohenstein ◽  
Norbert Weiss ◽  
...  
Keyword(s):  
Alternative Pathway ◽  
Fold Increase ◽  
Epidemiological Studies ◽  
Bilateral Nephrectomy ◽  
Sample Collection ◽  
Plasma Adma ◽  
Liquid Chromatography Tandem Mass ◽  
Alanine:Glyoxylate Aminotransferase

Background Multiple epidemiological studies demonstrated increased levels of an endogenous inhibitor of nitric oxide synthases asymmetric dimethylarginine (ADMA) in cardiovascular diseases. In addition to the well characterized pathway of ADMA hydrolysis by dimethylarginine dimethylaminohydrolase (DDAH) ADMA can also be metabolized through an alternative pathway by alanine:glyoxylate aminotransferase 2 (AGXT2), which converts ADMA to α-keto-δ-(N,N-dimethylguanidino)valeric acid (DMGV). The goal of this study was to better characterize the role of AGXT2 pathway in metabolism of ADMA in vivo using a recently developed assay for detection of DMGV in biological samples. Methods ADMA (250 μmol x kg-1 x d-1) was infused in C57/BL6 mice for 3 days using osmotic minipumps implanted intraperitoneally. We performed bilateral nephrectomy in some of the mice 24 hours before the end of ADMA infusion and sample collection. Urine was collected for 24 hours in metabolic cages. Blood was collected by cardiac puncture. Measurements of ADMA and DMGV were performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results Intraperitoneal infusion of ADMA for 3 days resulted in an increase in plasma ADMA levels from 0.46±0.045 to 1.57±0.40 μM (p<0.05) and in urine ADMA levels from 36.4±3.4 to 188.6±31.5 μmol / mmol creatinine (p<0.05). Elevation of ADMA concentration coincided with elevation of plasma DMGV levels from 0.21±0.025 to 0.61±0.14 μM (p<0.05) and urine DMGV levels from 41.4±3.2 to 162.5±32.9 μmol / mmol creatinine (p<0.05). Bilateral nephrectomy in the mice, which underwent ADMA infusion, lead to a 1.7 fold increase in plasma ADMA levels and a 17.6 fold increase in DMGV levels compared with the mice from the sham group. Conclusions Infusion of ADMA leads to increased flux through the AGXT2 pathway of ADMA metabolism in vivo. The observation that each 1 μmol / mmol creatinine increase in ADMA level in urine leads to a ~1 μmol / mmol creatinine increase in urine DMGV level suggests that AGXT2 is a major enzyme regulating ADMA levels in urine. The marked increase in DMGV levels in the mice lacking both kidneys suggests significant extrarenal production of DMGV in addition to absent renal excretion.

The role of asymmetric dimethylarginine in myocardial aging of aged rats and its mechanisms

2010 ◽  
Vol 34 (8) ◽  
pp. S29-S29
Author(s):  
Ru Zhang ◽  
Yong Zhen Gong ◽  
Wen Juan Xu ◽  
Yao Pan ◽  
Yan Xiong
Keyword(s):  
Asymmetric Dimethylarginine ◽  
Aged Rats ◽  
Myocardial Aging

Role of Asymmetric Dimethylarginine in Cardiorenal Syndrome

2014 ◽  
Vol 20 (14) ◽  
pp. 2448-2455 ◽  
Author(s):  
Seiji Ueda ◽  
Sho-ichi Yamagishi ◽  
Miyuki Yokoro ◽  
Seiya Okuda
Keyword(s):  
Asymmetric Dimethylarginine ◽  
Cardiorenal Syndrome

The Prominent Role of the Liver in the Elimination of Asymmetric Dimethylarginine (ADMA) and the Consequences of Impaired Hepatic Function

2008 ◽  
Vol 32 (6) ◽  
pp. 613-621 ◽  
Author(s):  
Milan C. Richir ◽  
Roderick H. Bouwman ◽  
Tom Teerlink ◽  
Michiel P.C. Siroen ◽  
Theo P.G.M. de Vries ◽  
...  
Keyword(s):  
Asymmetric Dimethylarginine ◽  
Hepatic Function ◽  
Impaired Hepatic Function

Role of Asymmetric Dimethylarginine (ADMA) in Diabetic Vascular Complications

2008 ◽  
Vol 14 (25) ◽  
pp. 2613-2618 ◽  
Author(s):  
Sho-ichi Yamagishi ◽  
Seiji Ueda ◽  
Kazuo Nakamura ◽  
Takanori Matsui ◽  
Seiya Okuda
Keyword(s):  
Asymmetric Dimethylarginine ◽  
Vascular Complications ◽  
Diabetic Vascular Complications

scholarly journals Role of asymmetric dimethylarginine in cardiovascular disease and diabetes

2008 ◽  
Vol 2 (4) ◽  
pp. 317-320 ◽  
Author(s):  
Guntram Schernthaner ◽  
Katarzyna Krzyzanowska
Keyword(s):  
Cardiovascular Disease ◽  
Asymmetric Dimethylarginine

scholarly journals The Role of Nitric Oxide, ADMA, and Homocysteine in The Etiopathogenesis of Preeclampsia—Review

2019 ◽  
Vol 20 (11) ◽  
pp. 2757 ◽  
Author(s):  
Weronika Dymara-Konopka ◽  
Marzena Laskowska
Keyword(s):  
Nitric Oxide ◽  
Asymmetric Dimethylarginine ◽  
Disease Process ◽  
Endothelial Activation ◽  
Morbidity And Mortality ◽  
Clinical Implications ◽  
Target Tissue ◽  
Vessel Involvement

Preeclampsia is a serious, pregnancy-specific, multi-organ disease process of compound aetiology. It affects 3–6% of expecting mothers worldwide and it persists as a leading cause of maternal and foetal morbidity and mortality. In fact, hallmark features of preeclampsia (PE) result from vessel involvement and demonstrate maternal endothelium as a target tissue. Growing evidence suggests that chronic placental hypoperfusion triggers the production and release of certain agents that are responsible for endothelial activation and injury. In this review, we will present the latest findings on the role of nitric oxide, asymmetric dimethylarginine (ADMA), and homocysteine in the etiopathogenesis of preeclampsia and their possible clinical implications.

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